Apoptosis and Bax Expression are Increased by Coal Dust in the Polycyclic Aromatic Hydrocarbon-Exposed Lung

Abstract

BackgroundMiners inhaling respirable coal dust (CD) frequently develop coal workers’ pneumoconiosis, a dust-associated pneumoconiosis characterized by lung inflammation and variable fibrosis. Many coal miners are also exposed to polycyclic aromatic hydrocarbon (PAH) components of diesel engine exhaust and cigarette smoke, which may contribute to lung disease in these workers. Recently, apoptosis was reported to play a critical role in the development of another pneumoconiosis of miners, silicosis. In addition, CD was reported to suppress cytochrome P450 1A1 (CYP1A1) induction by PAHs.MethodsWe investigated the hypothesis that apoptosis plays a critical role in lung injury and down-regulation of CYP1A1 induction in mixed exposures to CD and PAHs. We exposed rats intratracheally to 0.0, 2.5, 10.0, 20.0, or 40.0 mg/rat CD and, 11 days later, to intraperitoneal β-naphthoflavone (BNF), a PAH. In another group of rats exposed to CD and BNF, caspase activity was inhibited by injection of the pan-caspase inhibitor Q-VD-OPH [quinoline-Val-Asp (OMe)-CH2-OPH].ResultsIn rats exposed to BNF, CD exposure increased alveolar expression of the proapoptotic mediator Bax but decreased CYP1A1 induction relative to BNF exposure alone. Pan-caspase inhibition decreased CD-associated Bax expression and apoptosis but did not restore CYP1A1 activity. Further, CD-induced lung inflammation and alveolar epithelial cell hypertrophy and hyperplasia were not suppressed by caspase inhibition.ConclusionsCombined BNF and CD exposure increased Bax expression and apoptosis in the lung, but Bax and apoptosis were not the major determinants of early lung injury in this model.

Differential Gene Expression Induced by Exposure of Captive Mink to Fuel Oil: A Model for the Sea Otter

“…Degenerate primers were designed based upon multi-species alignments (GenBank) ( Table 1). The six systems were selected based on petroleum oil's-or components of petroleum oil's-known effect on immune defense (Schwartz et al, 2004ab), cellular injury (Ghanem et al, 2006), signal transduction (Burchiel et al, 2004), xenobiotic and metal metabolism (Schwartz et al, 2004ab), tumorigenesis (Ramesh et al, 2004), and reproduction (Mazet et al, 2001). Briefly, degenerate primer pairs were utilized on cDNA generated from three mink spleen samples.…”

Agmatine Ameliorates Nicotine Induced Lung Injury in Rats through Decrease TGF-ß1 and Bax Immunoexpression and by Anti-oxidative Sress Pathway: Histological, Immunohistochemical and Biochemical Study

“…The increased expression of Bax was detected in COPD lungs [60] indicating that NIC can activate apoptosis. Also, Bax expression and the associated apoptosis was increased in polycyclic aromatic hydrocarbon exposed Lung [18]. Immuno-histochemical assessment of Bax in lung tissue relates well with apoptotic process and the expression of other apoptosis mediators [61].…”

“…Apoptosis plays an essential part in the inflammatory processes [18]. One of the apoptotic activators is Bax, which is an integral membrane protein that bound to or associated with cytoplasmic organelles and can responds to various stimuli through migration to the mitochondria.…”

Gene transcription in sea otters (Enhydra lutris); development of a diagnostic tool for sea otter and ecosystem health

“…Herein, we describe the development of species‐specific quantitative real‐time polymerase chain reaction (qPCR) assays to measure differential transcript levels of multiple genes in the sea otter, and subsequent establishment of a ‘reference’ range for each of 10 genes of interest in peripheral blood leucocytes. The genes described are fundamental to mediation of detoxification and immune function (Schwartz et al 2004a,b), cellular injury (Ghanem et al. 2006), signal transduction (Burchiel & Luster 2001), xenobiotic metabolism (Schwartz et al.…”